The objective of the proposed research is to develop an efficient microbial process for commercial production of a polyphenolic protein adhesive similar to that produced by the mussel Mytilis edulis. Unlike most adhesives, this strong adhesive can set and adhere to surfaces in wet environments. Thus, it is likely to have application in dental restorations, as a surgical soft tissue adhesive, and in a variety of other medical applications. The natural mussel adhesive protein (MW 130,000) has been purified and characterized, and short analogs have been chemically synthesized. However, the most cost-effective method to produce a high molecular weight protein with the properties of the natural protein adhesive will undoubtedly be microbial production from a cloned gene. In Phase I Genex proposes to clone a cDNA sequence encoding the mussel adhesive protein using Mytilis edulis phenol gland mRNA. In Phase II, the adhesive protein will be expressed in a microbial production strain, methods for hydroxylation and curing will be developed, and the adhesive properties and potential applications will be assessed.